HMCES_XENLA
ID HMCES_XENLA Reviewed; 336 AA.
AC Q6IND6;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 54.
DE RecName: Full=Abasic site processing protein HMCES {ECO:0000250|UniProtKB:Q96FZ2};
DE AltName: Full=Embryonic stem cell-specific 5-hydroxymethylcytosine-binding protein;
DE Short=ES cell-specific 5hmC-binding protein {ECO:0000250|UniProtKB:Q96FZ2};
DE AltName: Full=Peptidase HMCES {ECO:0000250|UniProtKB:Q8R1M0};
DE EC=3.4.-.- {ECO:0000250|UniProtKB:Q8R1M0};
DE AltName: Full=SRAP domain-containing protein 1 {ECO:0000250|UniProtKB:Q96FZ2};
GN Name=hmces {ECO:0000250|UniProtKB:Q96FZ2};
GN Synonyms=srapd1 {ECO:0000250|UniProtKB:Q96FZ2};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Oocyte;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Sensor of abasic sites in single-stranded DNA (ssDNA)
CC required to preserve genome integrity by promoting error-free repair of
CC abasic sites. Acts as an enzyme that recognizes and binds abasic sites
CC in ssDNA at replication forks and chemically modifies the lesion by
CC forming a covalent cross-link with DNA: forms a stable thiazolidine
CC linkage between a ring-opened abasic site and the alpha-amino and
CC sulfhydryl substituents of its N-terminal catalytic cysteine residue.
CC The HMCES DNA-protein cross-link is then degraded by the proteasome.
CC Promotes error-free repair of abasic sites by acting as a 'suicide'
CC enzyme that is degraded, thereby protecting abasic sites from
CC translesion synthesis (TLS) polymerases and endonucleases that are
CC error-prone and would generate mutations and double-strand breaks. Has
CC preference for ssDNA, but can also accommodate double-stranded DNA with
CC 3' or 5' overhang (dsDNA), and dsDNA-ssDNA 3' junction (By similarity).
CC Acts as a protease: mediates autocatalytic processing of its N-terminal
CC methionine in order to expose the catalytic cysteine (By similarity).
CC {ECO:0000250|UniProtKB:Q8R1M0, ECO:0000250|UniProtKB:Q96FZ2}.
CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000250|UniProtKB:Q96FZ2}.
CC Note=Recruited to chromatin following DNA damage. Localizes to
CC replication forks. {ECO:0000250|UniProtKB:Q96FZ2}.
CC -!- DOMAIN: Glu-129 is involved in sensing abasic sites in single-stranded
CC DNA (ssDNA). His-203 stabilizes the abasic sites by forming a hydrogen
CC bond with the O4' hydroxyl group. {ECO:0000250|UniProtKB:P76318}.
CC -!- SIMILARITY: Belongs to the SOS response-associated peptidase family.
CC {ECO:0000305}.
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DR EMBL; BC072347; AAH72347.1; -; mRNA.
DR RefSeq; NP_001085145.1; NM_001091676.1.
DR AlphaFoldDB; Q6IND6; -.
DR SMR; Q6IND6; -.
DR DNASU; 432224; -.
DR GeneID; 432224; -.
DR KEGG; xla:432224; -.
DR CTD; 432224; -.
DR Xenbase; XB-GENE-6255746; hmces.L.
DR OrthoDB; 1487237at2759; -.
DR Proteomes; UP000186698; Chromosome 4L.
DR Bgee; 432224; Expressed in testis and 19 other tissues.
DR GO; GO:0005657; C:replication fork; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0045830; P:positive regulation of isotype switching; ISS:UniProtKB.
DR GO; GO:0018142; P:protein-DNA covalent cross-linking; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.90.1680.10; -; 1.
DR InterPro; IPR003738; SRAP.
DR InterPro; IPR036590; SRAP-like.
DR PANTHER; PTHR13604; PTHR13604; 1.
DR Pfam; PF02586; SRAP; 1.
DR SUPFAM; SSF143081; SSF143081; 1.
PE 2: Evidence at transcript level;
KW Autocatalytic cleavage; Chromosome; Covalent protein-DNA linkage;
KW DNA damage; DNA-binding; Hydrolase; Protease; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q8R1M0"
FT CHAIN 2..336
FT /note="Abasic site processing protein HMCES"
FT /id="PRO_0000164399"
FT REGION 26..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 285..336
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 26..40
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 2
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
FT SITE 129
FT /note="Required for sensing abasic sites"
FT /evidence="ECO:0000250|UniProtKB:P76318"
FT SITE 203
FT /note="Required to stabilize abasic sites"
FT /evidence="ECO:0000250|UniProtKB:P76318"
FT MOD_RES 2
FT /note="Thiazolidine linkage to a ring-opened DNA abasic
FT site"
FT /evidence="ECO:0000250|UniProtKB:Q96FZ2"
SQ SEQUENCE 336 AA; 38280 MW; 4FBF0A62A7AE1E9D CRC64;
MCGRTACTLA PDDVSKACSY QDKQGRQKCP KWRDGDTDKY QPSYNKSPQS NNPVLLSLKH
FQKDADSSER VLAAMRWGLI PSWFNELDPS KMQYKTNNCR SDTITEKALY KAPLFKGRRC
VVLADGFYEW KRQDGEKQPY YIYFPQIKSE KFPEEQDMMD WNGQRLLTMA GLFDCWEPPS
GGEPLYSYTV ITVDSSKTMN CIHDRMPAIL DGDEAIRKWL DFGEVSTQDA LKLIHPIENI
TYHPVSTVVN NSRNNSTECI AAVILTQKKG PALSASSKKM LEWLQNKSPK KEESRSIIQS
PKLSQFGAPP KKTSAGLMQQ WLKKEDGEPS PKRAKK
